crossing96/oncoscreening huggingface dataset:
MFSD12, transcriptionally regulated by PLAGL2, promotes bladder cancer progression.	Bladder cancer (BLCA) is one of the most common malignant tumors of the urinary system. Identification of novel molecular signaling targets for the tumorigenesis of BLCA is important. Data from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases suggest that major facilitator superfamily domain containing 12 (MFSD12) may act as an important oncogene in BLCA. MFSD12 expression is confirmed to be elevated in BLCA patients. Genetic manipulation of MFSD12 mediated by Tet-inducible lentiviral expression vector is conducted in two BLCA cell lines, including UMUC3 and 5637. Following this manipulation, the cells are subjected to treatment with or without doxycycline. Our results show that MFSD12 knockdown inhibits cell proliferation, migration, and invasion, and arrests the G1 stage-induced cell cycle. Furthermore, silencing of MFSD12 reduces lung metastatic lesions and xenografted tumor formation of BLCA cells. To further explore the effect of MFSD12 on BLCA cells, transcriptomics and metabolomics analyses are performed on MFSD12-overexpressing cells. Subsequently, luciferase reporters and chromatin immunoprecipitation (ChIP)-PCR assays reveal that MFSD12 is regulated positively by pleomorphic adenoma gene like-2 (PLAGL2), an important transcription factor. Collectively, our results indicate that MFSD12 exerts a tumor-promoting effect on BLCA progression, under the modulation of transcription factor PLAGL2.	bladder
STAG2 regulates polycomb and differentiation in urothelial precursors and bladder cancer.	The STAG2 tumor suppressor gene is commonly inactivated by mutations in a wide range of common cancer types. STAG2 encodes a component of the cohesin complex, which controls sister chromatid cohesion and 3D genome organization. In bladder cancer, STAG2 mutations are most common in the earliest low-grade lesions, suggesting that mutational inactivation of STAG2 may be an initiating event. To provide insight into the mechanisms of STAG2 tumor suppression in bladder cancer, siRNA and shRNA were used to knock down STAG2 in several different human non-neoplastic bladder cancer precursor cell lines. Gene editing was used to generate cultured human cancer cell lines that differ only in the presence or absence of bladder-cancer derived STAG2 mutations. These systems were interrogated using RNA-seq, Western blot, and qRT-PCR before and after induced differentiation. We find that inactivation of STAG2 in bladder cancer cells and in bladder epithelial precursor cells resulted in concomitant inactivation of the H3K27me3 Polycomb chromatin mark. Inactivation of STAG2 also attenuated induced differentiation of bladder epithelial precursor cells. STAG2 and other components of cohesin were upregulated during this differentiation process. This study provides new insights into the role of STAG2 in the pathogenesis of bladder cancer, demonstrating roles for STAG2 in the regulation of Polycomb-mediated epigenetic regulation and in the differentiation of bladder epithelial precursor cells.	bladder
MiR-20a-5p Inhibits Bladder Cancer Proliferation and Migration by Targeting KPNA2.	Bladder cancer (BC) is one of the 10 most common cancers in the world, and its recurrence and metastasis are the main causes of death in BC patients. Exploring the molecular mechanisms of BC pathogenesis and searching for new prognostic markers and therapeutic targets are important for improving patient prognosis. KPNA2 was found to be a potential oncogene in different malignant tumours, as demonstrated in our previous study. To better understand the mechanisms associated with BC development, we investigated the inhibitory effect of miR-20a-5p on the oncogene KPNA2. RNA-seq data from BC patients were downloaded through the TCGA database for bioinformatics analysis, including gene expression, co-expression analysis, GSEA, nomogram modelling, functional enrichment analysis, WGCNA, GO and KEGG to assess the potential biological functions of miR-20a-5p in BC. Subsequently, we further verified the expression of miR-20a-5p in BC cells by RT-qPCR, and in vitro experiments were performed to investigate the effects of this gene on BC cell proliferation and migration. MiR-20a-5p was downregulated in BC tissues and cells. Kaplan-Meier analysis revealed that the higher the expression of miR-20a-5p in patients, the higher the survival rate of BC patients. MiR-20a-5p overexpression inhibited the proliferation and migration of BC cells. In addition, miR-20a-5p can directly bind to nuclear transporter protein α2 (KPNA2) in cells, targeting and regulating the expression of KPNA2. These findings indicate that miR-20a-5p targeting KPNA2 adversely affects the proliferation and migration of BC cells, suggesting that miR-20a-5p may be an attractive target in BC therapy.	bladder
The lncRNA MIR4435-2HG Modulates Bladder Cancer Progression and Ferroptosis Through the IQGAP3/Ras/ERK/CREB Pathway.	Bladder cancer (BCa) is characterized by high incidence and recurrence rates, and its development is closely related to ferroptosis. However, the regulatory mechanism of MIR4435-2HG in BCa and ferroptosis remains unclear. This study investigated the role of the long non-coding RNA (lncRNA) MIR4435-2HG in BCa progression and ferroptosis regulation through the IQ motif containing GTPase activating protein 3 (IQGAP3)/rat sarcoma (Ras)/extracellular signal-regulated kinase (ERK)/cAMP response element-binding protein (CREB) axis. Bioinformatics analysis of TCGA-BLCA data (402 tumors, 19 normals) was integrated to establish clinical relevance. Bladder cancer T24 cells were transfected with an overexpression vector (OE-MIR4435-2HG) or a knockdown vector (sh-MIR4435-2HG). Various assays, including cell counting kit-8 (CCK-8), scratch, transwell, flow cytometry, enzyme-linked immunosorbent assay (ELISA), and Western blotting, were subsequently utilized to assess cellular behavior and protein expression. Finally, a subcutaneous xenograft model was employed for in vivo validation. TCGA analysis revealed MIR4435-2HG overexpression in tumors (log2FC = 3.21, p < 0.0001), association with reduced survival (HR = 1.68, p = 0.006), and enrichment in Basal subtypes. Overexpression of MIR4435-2HG promoted the migration, invasion, and proliferation of bladder cancer cells, with increased Ki-67 and cytoskeleton-associated protein 4 (CKAP4) protein expression, whereas MIR4435-2HG knockdown had the opposite effects. MIR4435-2HG overexpression activated the IQGAP3/Ras/ERK/CREB signaling axis, reducing the protein levels of IQGAP3, Ras, ERK, and CREB while increasing the expression of ferroptosis markers, specifically malondialdehyde (MDA), lipid peroxidation (LPO), and reactive oxygen species (ROS). MIR4435-2HG knockdown reversed these changes. In vivo, overexpression of MIR4435-2HG significantly enhanced tumor growth, whereas its suppression markedly reduced tumor volume and weight. The ferroptosis activator RSL3 further attenuated tumor progression in both the knockdown and overexpression models, and combined treatment with the ERK inhibitor SCH772984 synergistically suppressed tumor growth in MIR4435-2HG-overexpressing xenografts. Consistent with the in vitro findings, MIR4435-2HG modulated the IQGAP3/Ras/ERK/CREB axis and ferroptosis markers (ROS, MDA, LPO, glutathione peroxidase 4 (GPX4)) in vivo, reinforcing its role in promoting malignancy and ferroptosis resistance. Treatment of OE-MIR4435-2HG-transfected cells with SCH772984 further reduced protein levels and cell viability. Notably, RSL3 diminished IQGAP3, Ras, ERK, CREB, and GPX4 levels across the experimental conditions. These findings indicate that MIR4435-2HG is a pivotal regulator of bladder cancer progression and ferroptosis via the IQGAP3/Ras/ERK/CREB axis, suggesting that MIR4435-2HG is a potential therapeutic target for intervention.	bladder
Comprehensive Assessment of Tumor Stromal Heterogeneity in Bladder Cancer by Deep Learning and Habitat Radiomics.	RATIONALE AND OBJECTIVES: Tumor stromal heterogeneity plays a pivotal role in bladder cancer progression. The tumor-stroma ratio (TSR) is a key pathological marker reflecting stromal heterogeneity. This study aimed to develop a preoperative, CT-based machine learning model for predicting TSR in bladder cancer, comparing various radiomic approaches, and evaluating their utility in prognostic assessment and immunotherapy response prediction. METHODS: A total of 477 bladder urothelial carcinoma patients from two centers were retrospectively included. Tumors were segmented on preoperative contrast-enhanced CT, and radiomic features were extracted. K-means clustering was used to divide tumors into subregions. Radiomics models were constructed: a conventional model (Intra), a multi-subregion model (Habitat), and single-subregion models (HabitatH1/H2/H3). A deep transfer learning model (DeepL) based on the largest tumor cross-section was also developed. Model performance was evaluated in training, testing, and external validation cohorts, and associations with recurrence-free survival, CD8+ T cell infiltration, and immunotherapy response were analyzed. RESULTS: The HabitatH1 model demonstrated robust diagnostic performance with favorable calibration and clinical utility. The DeepL model surpassed all radiomics models in predictive accuracy. A nomogram combining DeepL and clinical variables effectively predicted recurrence-free survival, CD8+ T cell infiltration, and immunotherapy response. Imaging-predicted TSR showed significant associations with the tumor immune microenvironment and treatment outcomes. CONCLUSION: CT-based habitat radiomics and deep learning models enable non-invasive, quantitative assessment of TSR in bladder cancer. The DeepL model provides superior diagnostic and prognostic value, supporting personalized treatment decisions and prediction of immunotherapy response.	bladder
The promising arsenal of ferroptosis inducers in bladder cancer.	Bladder cancer ranks among the most common malignancies of the urinary system. Despite continuous advances in treatment technologies, the risk of tumor progression and metastasis remains high due to its extreme heterogeneity, resulting in poor patient prognosis. Patients with muscle-invasive bladder cancer face the greatest challenges. Immediate clinical treatment is radical cystectomy after the administration of neoadjuvant therapy. The effect of different conventional chemotherapeutic drugs is heavily impaired by tumor resistance. In turn, the research of effective therapeutic approaches to prevent resistance of malignant tumors has turned out to be the most important clinical concern in the management of bladder cancer. Ferroptosis is another type of programmed cell death that is morphologically and mechanistically different than apoptosis and necrosis. To maintain high rates of proliferation, bladder cancer cells are hypernormal to iron-dependent oxidative stress. So using the ferroptosis inducers to destabilize their vulnerable antioxidant defenses provides a very specific targeting approach to the weaknesses of this natural metabolic homeostasis. Inductors of ferroptosis (erastin, artemisinin, conjugated polymer nanoparticle, quinazoline-aromatic urea analogue derivatives, etc.) show great potential in improving the efficacy of traditional anticancer drugs used to fight against bladder cancer. Preclinical studies combining standard therapies with ferroptosis-related treatments have yielded promising results. However, clinical trials targeting ferroptosis in bladder cancer remain scarce, posing challenges for translating these findings into clinical practice. In this review, we aim to highlight the latest advances in ferroptosis induction as a therapeutic strategy for bladder cancer. It provides a reference for subsequent research and additional insights into the development and validation of corresponding drugs for bladder cancer treatment.	bladder
RNA m(5)C Modifications in the Development and Prognosis of Muscle-Invasive Bladder Cancer.	The m(5)C RNA modifications have been implicated in the pathogenesis of urothelial carcinoma and hold potential as prognostic biomarkers for muscle-invasive bladder cancer (MIBC) patients. In this study, we developed an MIBC-risk model by integrating m(5)C modification-related genes and differentially expressed genes using Nanopore sequencing and a machine learning approach. Compared to our previous research, we observed that m(5)C modifications are more functional, with the most enriched regions being the 3'UTR and exons. Our analysis revealed differential m(5)C methylation sites in several well-characterized cancer-related genes, including BMI1, PTEN, MALAT1, FADD, STAT5A, BIRC6, FOXO3, CCNG1, PAK2, UBE2L3, SMARCB1, and TUG1. Functional enrichment analysis demonstrated significant involvement of these genes in key oncogenic pathways, particularly DNA damage response, double-strand break repair, p53 signaling, MAPK cascade, NF-κB signaling, and cell proliferation/migration pathways. Unlike models based on single factors, the combination of m(5)C modification-related genes and differentially expressed genes resulted in a more effective classification model. This approach yielded an optimized 11-gene prognostic signature comprising GGA1, NUMBL, ECHDC2, NLRC5, EIF2D, GJA1, XPC, DAZAP2, C6orf120, WDR45, and CES1, which demonstrated superior predictive performance in TCGA MIBC patients. These findings establish m(5)C RNA modification patterns as promising molecular signatures for MIBC prognosis and potential therapeutic targets.	bladder
Methylparaben and propylparaben promote bladder cancer invasion via MMP2 and PPARG modulation.	OBJECTIVE: Parabens, esters of p-hydroxybenzoic acid, are widely utilized as antimicrobial preservatives in consumer products. While increasing evidence implicates parabens in tumor progression across cancers, their role and mechanisms in bladder cancer (BLCA) remain uncharacterized. METHODS: Methylparaben (MP) and propylparaben (PP) effects on invasion, migration, and proliferation were assessed in BLCA T24 and SW780 cells. The above effects have also been verified through in vivo experiments. Genes linked to MP, PP, and BLCA were curated from public databases. Hub genes were identified through protein-protein interaction (PPI) networks and an optimized prognostic model using 101 machine learning algorithms. Molecular docking (MD) and molecular dynamics simulations (MDS) evaluated hub gene-paraben interactions, followed by functional validation via transfection assays. RESULTS: MP and PP significantly enhanced BLCA cell invasion (all P < 0.05) without affecting proliferation or migration. It can also promote tumor growth in nude mice (all P < 0.05). Network toxicology and prognostic modeling identified MMP2 and PPARG as key targets for MP and PP, respectively. MD/MDS confirmed stable binding between parabens and their targets. MP upregulated MMP2 expression, while PP downregulated PPARG (all P < 0.05). MMP2 knockdown and PPARG overexpression partly reversed paraben-induced invasion (all P < 0.05). CONCLUSION: This study reveals that MP and PP promote BLCA invasion via MMP2 and PPARG modulation, providing mechanistic insights into paraben-associated tumorigenesis and underscoring potential public health implications of paraben exposure. These findings have raised concerns about the risk of BLCA caused by low level environmental exposure to parabens, especially among people with impaired detoxification pathways.	bladder
Targeting PSMB5-induced PANoptosis in bladder cancer: multi-omics insights and TCM candidate discovery.	BACKGROUND: Bladder cancer (BLCA) is among the most common malignancies worldwide, with significant mortality rates. The function of PANoptosis in BLCA, as a controlled process of programmed cell death, remains largely unelucidated. The study aimed to elucidate the role of PANoptosis-related genes in BLCA and investigate their molecular mechanisms, prognostic significance, and therapeutic potential. METHODS: By analyzing differentially expressed genes in BLCA from The Cancer Genome Atlas (TCGA) and PANoptosis-associated genes, we discovered 98 genes associated with PANoptosis. Functional enrichment and consensus clustering identified molecular subtypes linked to these genes. A prognostic model was developed via LASSO regression based on these genes. Subsequent analyses assessed clinical significance, characteristics of the immunological milieu, and treatment responsiveness. Systematic screening with machine learning (ML) identified PSMB5 as a pivotal gene, with its functional importance further clarified using single-cell sequencing and Mendelian randomization analysis (MR). In vitro research confirmed the biological activities of PSMB5 in BLCA. Molecular docking demonstrated PSMB5's binding affinity with traditional Chinese medicines (TCMs). RESULTS: Clustering of 98 PANoptosis-associated genes revealed molecular subgroups A and B. A prognostic approach identified high-risk and low-risk cohorts, revealing considerable disparities in clinical characteristics and immunological landscapes across the groups. ML and MR identified PSMB5 as a risk factor in BLCA. Single-cell sequencing revealed that PSMB5 expression is predominantly associated with three cell lines linked to lymph node metastases. In vitro findings demonstrated that PSMB5 knockdown inhibited the proliferation and migration of BLCA cells while promoting apoptosis, whereas overexpression has the opposite effect. Molecular docking revealed a robust binding affinity between PSMB5 and five TCMs. CONCLUSIONS: A prognostic model incorporating PANoptosis-related genes was developed for stratifying BLCA risk and assessing the immune microenvironment. PSMB5 has been recognized as a crucial therapeutic target, exhibiting dual importance in the molecular etiology of BLCA and traditional Chinese medicine intervention.	bladder
Mitochondria-located circRCP regulates redox homeostasis via stabilizing LRPPRC/SLIRP complex to promote bladder urothelial carcinoma tumorigenesis.	The function of circular RNAs (circRNAs) located within the mitochondria in the pathogenesis of urothelial carcinoma of the bladder (UCB) remains largely unexplored. This study identified a mitochondria-located circRNA named circRCP from the nuclear genome of UCB cells. It is frequently upregulated in UCB and serves as an independent prognostic factor. This study further illustrates that circRCP enhances UCB tumorigenesis by regulating intracellular redox homeostasis. The knockdown of circRCP heightens mitochondrial oxidative stress, which leads to ROS generation, consequently triggering UCB cell apoptosis. Mechanistically, by forming a circRCP/LRPPRC/SLIRP RNA-protein ternary complex, circRCP enhances the LRPPRC/SLIRP stability and protects LRPPRC from ubiquitination and proteasomal degradation. Clinically, UCBs exhibiting high circRCP and LRPPRC expression had the worst outcomes. Taken together, we have identified a mitochondria-located circRNA that protects UCB cells from oxidative stress, highlighting its potential role in UCB pathogenesis and warranting further investigation into its therapeutic applicability.	bladder
Management of Bladder Cancer During Pregnancy: A Narrative Review.	"BACKGROUND/AIM: Bladder cancer (BC) during pregnancy is extremely rare. Therefore, the epidemiological understanding of BC during pregnancy remains limited, and the literature consists mostly of isolated case reports. This review aimed to provide an updated, comprehensive overview of the incidence, risk factors, and clinical management of BC during pregnancy, based on published case reports and the literature. MATERIALS AND METHODS: A literature search was performed on 1st July 2025 using PubMed, EMBASE, and Google Scholar with no date limit. The following terms were used: ""bladder cancer"", ""urothelial carcinoma"", ""bladder tumor"", ""treatment"", ""management"", ""pregnancy"", ""pregnant women"" and ""therapy"". Finally, 18 articles were included. RESULTS: Pregnancy introduces a complex clinical scenario, where overlapping symptoms can complicate diagnosis. While hematuria may often be attributed to benign pregnancy-related causes, persistent or unexplained presentations should prompt further assessment to exclude underlying malignancy. Cystoscopy remains the gold standard for diagnosing BC, offering direct visualization and the possibility of biopsy. However, it is an invasive procedure and is associated with potential discomfort and complications, which can be particularly concerning during pregnancy. Non-invasive techniques, such as ultrasound and magnetic resonance imaging, are preferred for diagnostic evaluation as they minimize radiation exposure and are generally considered safe in pregnancy. CONCLUSION: The treatment of BC during pregnancy poses a significant clinical challenge, requiring a delicate balance between optimizing maternal outcomes and ensuring fetal safety. Therapeutic decisions are largely guided by two key factors: the gestational age at diagnosis and the clinical stage of the tumor. Radical surgical interventions and systemic therapies are generally contraindicated during pregnancy due to potential risks to the fetus. Therefore, a conservative approach is often adopted, aiming to contain disease progression while minimizing harm to the developing fetus."	bladder
Real-world Outcomes of Enfortumab Vedotin in Elderly Patients With Metastatic Urothelial Carcinoma.	BACKGROUND/AIM: Enfortumab vedotin (EV) is an antibody-drug conjugate approved for metastatic urothelial carcinoma (mUC); however, clinical data in elderly patients are limited. Given the increasing use of EV as a first-line or subsequent treatment, assessing its safety and efficacy in older populations is crucial. PATIENTS AND METHODS: This retrospective, multi-institutional study evaluated the safety and efficacy of EV in patients aged ≥80 years with platinum-refractory mUC. Clinical outcomes were compared with those in patients aged <80 years. Propensity score matching (PSM) was used to minimize selection bias. RESULTS: Among 129 patients included, 25 (19%) were aged ≥80 years. Median follow-up was 7.7 months. There were no significant differences in overall survival (OS: 14.7 vs. 8.9 months, p=0.411), progression-free survival (PFS: 10.2 vs. 6.5 months, p=0.972), or objective response rate (ORR: 56% vs. 46%, p=0.248) between older and younger patients. Rates of treatment discontinuation and dose reduction were comparable between patients aged ≥80 and those aged <80 years, with no statistically significant differences (8% vs. 13%, p=0.529; 28% vs. 21%, p=0.438). CONCLUSION: EV demonstrated comparable efficacy and tolerability in patients aged ≥80 years relative to younger counterparts. These findings support the safe and effective use of EV in elderly patients with mUC and highlight the need for further prospective studies in this population.	bladder